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PMID: 6192443 Published · ppublish English Case Reports Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 80 ·No. 15 ·1983-08-00 ·Pages 4842-6

Charache S, Dover G, Smith K, Talbot CC, Moyer M, Boyer S

Abstract

Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes.

MeSH Terms

Adult Anemia, Sickle Cell/drug therapy,genetics Azacitidine/therapeutic use DNA/genetics,isolation & purification DNA Restriction Enzymes Fetal Hemoglobin/genetics Genes/drug effects Globins/genetics Humans Male Methylation Nucleic Acid Hybridization

Chemicals

Globins DNA Fetal Hemoglobin DNA Restriction Enzymes Azacitidine

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Charache S

Dover G

Smith K

Talbot C C

Moyer M

Boyer S

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36 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.80.15.4842

Published

1983-08-00

Pages

4842-6

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC384141

Subset

Grants

NHLBI NIH HHS · HL027996 · United States

NHLBI NIH HHS · HL15026 · United States

NHLBI NIH HHS · HL28028 · United States

External Links

PubMed source DOI: 10.1073/pnas.80.15.4842 PMC Full Text View journal details

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Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

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